Solid tumor growth proceeds in concert with tumor vascularization, which requires as essential components, endothelial cells of the host capillary system and a tumor-produced mitogenic substance, the angiogenesis factor (AF). We have developed an in vitro model system, in which cultured endothelial cells from fetal bovine aorta show a stimulation in growth response to tumor-derived substances present in the medium. We propose to examine various aspects of the phenomenon of tumor vascularization using this in vitro model system. These features include studies on the purification and characterization of the tumor AF from the Walker 256 carcinoma, on the relationship of this agent(s) to AF from other tumors and to other known cellular growth factors, on the production and release of the tumor AF, on actual or potential antiangiogenic agents, and on the mechanisms of action by which these growth factors (both stimulators and inhibitors) affect endothelial cell growth. A tumor-derived agent(s) that has been purified about 10 to the third power fold with an overall yield greater than 10% is active in both in vitro and in vivo (rabbit corneal implant and chicken chorioallantoic membrane (CAM) assays. The activity contained in conditioned medium from cultured Walker tumor cells appears to be released selectively and is subject to control by various agents. Potential antiangiogenic agents, plasmin/plasminogen, platelet-derived growth factor, and vitreous factors, have been screened by our in vitro procedures and are being investigated further by in vivo (mainly CAM) techniques. In sum the thrust of these efforts is to better understand the entire process of tumor vascularization, and ultimately to be able to control this process and consequently tumor growth as well as spread.